Lackey was one of five players traded by Boston on Thursday.
Ranaudo, 24, was recently ranked the sixth-best Red Sox prospect in MLB.com's rankings.
With Lester and Lackey both gone, the rotation is suddenly full of young pitchers.
Ranaudo might be sent back to Triple-A Pawtucket after his debut, as Boston currently has Clay Buchholz, Joe Kelly, Brandon Workman, Allen Webster and Rubby De La Rosa in the rotation.
The Red Sox snagged Ranaudo with the 39th overall pick in the 2010 First-Year Player Draft. The New Jersey native grew up a Yankees fan, so perhaps it's appropriate he makes his debut against them.
In 21 starts for Pawtucket this season, Ranaudo is 12-4 with a 2.41 ERA.
Ian Browne is a reporter for MLB.com. Read his blog, Brownie Points, and follow him on Twitter @IanMBrowne. This story was not subject to the approval of Major League Baseball or its clubs.